Field of the Invention
The present invention relates to a method, a breathing apparatus and a computer program for prediction of fluid responsiveness of a subject undergoing mechanical ventilation.
Description of the Prior Art
Hemodynamic monitoring—i.e. the continuous display and recording of hemodynamic parameters to inform about the status of the cardiovascular system by means of specific devices—is a cornerstone in the care of critically ill patients. The main goal of hemodynamic monitoring is to assess the function of the cardiovascular system in order to diagnose and guide the treatment of any dangerous acute cardiovascular event. There is a general consensus among clinicians that organ function is preserved by maintaining a normal cardiovascular status in which oxygen delivery to the tissues largely matches their oxygen consumption. Cardiovascular instability compromises peripheral oxygen delivery and, if remained undetected or inappropriately treated, can affect normal tissue function and lead to organ failure. Hemodynamic monitoring is especially successful when it helps detecting any hemodynamic instability before organ dysfunction ensues and to monitor the magnitude and time of proactive therapeutic interventions aimed at preventing it. Thus, hemodynamic monitoring must be regarded as an essential component in the initial and continued management of all critically ill patients treated in the emergency, operating room and in the intensive care unit. Once organ dysfunction has ensued, hemodynamic monitoring and treatment alone are of little help in improving patient's outcome (Vincent J-L, Rhodes A, Perel A, Martin G S, Rocca Della G, Vallet B, Pinsky M R, Hofer C K, Teboul J-L, de Boode W-P, et al.: Clinical review: Update on hemodynamic monitoring—a consensus of 16. Crit Care 2011, 15:229, Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl Med J 2001; 345: 1368-1377, Bland R D, et al. Hemodynamic and oxygen transport patterns in surviving and non-surviving postoperative patients. Crit Care Med 1985; 13: 85-90, Connors A F, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. JAMA 1996; 276: 889-897).
One of the most important determinants of the status of the cardiovascular system is its effective volume of blood, or its volemia. There is a certain amount of blood within such system in a healthy state, called normovolemia or euvolemia, which is related to normal cardiovascular function and hence to an adequate delivery of oxygenated blood to all body tissues. In contrast, any decrease in intravascular volume or hypovolemia due to for example bleeding, dehydration, microcirculatory failure, third space fluid sequestration or excessive vasodilation may cause a deficit in oxygen delivery to tissues and if severe and/or prolonged enough may lead to organ failure. A concept inherent to volemia is preload. Preload is defined as the volume of blood within the ventricles at the end of diastole that stretch the myocardial fibers to a certain sarcomere length necessary for a normal effective and efficient heart muscle contraction during systole. Any decrease in cardiac preload will result in a decrease of the heart's efficiency and in systemic hypo-perfusion of different degrees, which can frequently coexist with normal standard hemodynamic parameters such as mean arterial or central venous pressure.
Standard hemodynamic monitoring systems can easily detect severe hypovolemic states but often fail in diagnosing moderate to mild hypovolemia. This is an important limitation in the monitoring of critical care patients because when such occult hypovolemia remains for many hours it can be associated with several complications such as acute renal failure, heart ischemia, cerebral stroke or wound infection among others. This occult hypovolemia is manifested as a “preload dependency” which in medical terms means that the cardiovascular system operates at the steep portion of the Frank-Starling relationship, illustrated in FIG. 1. According to this relationship the ventricle will respond with an increase in cardiac output (more often expressed as stroke volume SV or the volume ejected by the ventricle with each systole) in response to the administration of intravascular volume. In other words the patient is “fluid responsive”.
With reference to FIG. 1, the Frank-Starling relationship describes the relation between volemia (preload) and cardiac output (CO) or stroke volume (SV). In the volume responsive part, denoted by reference numeral (a), an increase in volemia will cause a corresponding increase in stroke volume. In a normovolemic patient the same increment in volume will only cause a very modest increase or no increase at all in SV, as illustrated by the scenario denoted by reference numeral (b). In a volume overloaded state (flat portion of the Frank-Starling relationship) any given volume will not affect SV but may lead to fluid overload of lungs and body.
An important distinction to be made here is that being fluid responsive does not necessarily mean that the patient is hypovolemic as fluid responsiveness is a normal physiological status due to the high capacitance of the venous system. It only tells us that the cardiovascular system will respond with a certain increase in CO to the administration of intravenous fluids.
Intravenous fluid administration is considered the first line intervention in hemodynamically unstable patients to restore euvolemia (or in other words, to optimize preload). There is established evidence that optimizing high-risk surgical patients by volume loading improves hemodynamics and decreases the incidence of postoperative complications and hospital mortality (Kim I B, Bellomo R, Fealy N, et al. A pilot study of the epidemiology and association of pulse pressure variation in cardiac surgery patients. Crit Care Resusc 2011; 13: 17-23, Gan T J, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002; 97: 820-6, Lopes M R, Oliveira M A, Lemos I P, et al. Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial. Crit Care 2007; 11: R100). However, only 50% of hemodynamically unstable patients are fluid responsive and it has been clearly established that an excess of intravenous fluids (i.e. over-resuscitation) is associated with an increased morbi-mortality as it can precipitate lung edema, worsen cor pulmonale or induce left heart failure, as discussed e.g. in Bellamy M C: Wet, dry or something else? British Journal of Anaesthesia 2006, 97:755-757 of the appended list of references.
Therefore, the routine assessment of fluid responsiveness (i.e. the prospective identification of patients in whom intravenous administration of fluids will improve hemodynamics) is becoming an essential component of goal-directed fluid therapy protocols aimed at both, optimizing the intravascular volume status and avoiding the deleterious consequences of fluid overload (Salzwedel C, Puig J, Carstens A, Bein B, Molnar Z, Kiss K, Hussain A, Belda J, Kirov M Y, Sakka S G, Reuter D A. Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study. Crit Care 2013; 17: R191, Brandstrup B, Tonnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid restriction on postoperative pulmonary complications: comparison of two perioperative fluid regiments: a randomized assessor-blinded multicenter trial Ann Surg 2003; 238: 641-8).